1. Technical Field
The present invention relates to an elution test for evaluating the elution properties of a specific component contained in a pharmaceutical preparation. More specifically, the present invention relates to an elution test method for measuring the volume of solution of a specific component from a preparation such as a tablet or a capsule in an elution test liquid in a state (environment) similar to the inside of a digestive tube in order to obtain the elution concentration of the specific component, and elution test apparatus used for the method.
2. Related Art
In general, a pharmaceutical preparation undergoes a change in the elution properties and efficacy when only the size of a tablet is changed although the shape of medicine is the same. Even in case the size is unchanged, a different coating on the surface of the medicine leads to a change in the elution properties and the efficacy. When placing on the market a pharmaceutical preparation containing a specific component, an elution test is required for evaluating the properties of elution of the specific component into an elution test liquid. In case the specific component is not eluted within a predetermined time, it is judged that the expected efficacy is not obtained. The elution test liquid refers to an elution test liquid being acid (around pH1), weak acid (around pH4), or neutral (around pH7). In particular, in the case of a preparation that requires an in vitro-in vivo correlation, it is recommended to use a neutral test liquid as per the FDA guideline.
In the development of a pharmaceutical preparation, various preparation prescriptions are studies to establish a preparation prescription having optimum elution properties of a specific component so that the specific component will deliver in vivo with an expected efficacy. Such being the background, an elution test in the development of a pharmaceutical preparation involves a large number of samples to be evaluated. The elution test is cumbersome and takes time in analysis. Thus, a speedup of elution test operation is an essential requirement in the development of a pharmaceutical preparation.
In general, an elution test method for a pharmaceutical is defined in the Japanese Pharmacopoeia. Although the Japanese Pharmacopoeia defines the operation procedure in its elution test method, it does not include details on a method for calculating the elution concentration of a pharmaceutical from the data obtained.
As methods for determining the volume of pharmaceutical generally include absorbance measurement method (UV method) and the liquid chromatography (HPLC method).
The absorbance measurement method fills a test liquid containing a specific component eluted from a preparation in a certain cell of glass or quartz, measures the absorbance of the test liquid at a predetermined wavelength with a spectrophotometer, and obtains the degree of elution based on the working curve. The liquid chromatography separates a specific component alone via the liquid chromatography technique from a test liquid containing the specific component eluted from a preparation and obtains the degree of elution from the absorbance of the specific component by using a spectrophotometer.
The absorbance measurement method is simple and accurate so that it is often employed in quality management tests for pharmaceuticals. Its merits include a short analysis time and a small running cost required in analysis. In case an impurity component other than the specific component is mixed in the preparation, it is difficult to selectively determine the specific component alone. The impurity component generally refers to a component that hinders determination of the volume of the specific component, such as an antoxidant (such as ascorbic acid) or antiseptic and milderproofing agents contained in the preparation as well as a pharmaceutical additive having absorption in the ultraviolet or visible area.
The liquid chromatography is capable of separating a plurality of components in a preparation and determining their volumes, with demerits including a long analysis time and a larger running cost. For a substance whose specific component tends to change, the specific component changes during analysis in the liquid chromatography method that requires a long analysis time, thus making it difficult to obtain a precise value.
Generally, an elution test of a pharmaceutical evaluates the elution process of a specific component A alone assuming that the specific component is A and does not need to evaluate a decompressed matter A′ that changed from the specific component A. However, in an elution test, concerning the specific component A that suffers from change, as an example, the volumes of the specific component A and the decompressed matter A′ that changed from the specific component A are determined to determine the total component volume A+A′, or the specific component A is converted to a decompressed matter A′ or their derivative A″ for measurement (refer to document Vo. 412, published by Federation of Pharmaceutical Manufacturers' Associations of Japan, “management of hardly-soluble pharmaceutical and variation pharmaceutical for the quality reevaluation”).
To determine the volume of a specific component A and the decomposed matter A′ that changed from the specific component A and obtain the total component volume A+A′, general approaches include a method of separating the specific component A present in an eluate and the decomposed matter A′ respectively by way of the HPLC method and obtaining the sum of their volumes, or a method of separating the specific component A present in an eluate and the decomposed matter A′ respectively by way of the HPLC method to determine only the volume of the specific component A and correcting the volume of change from the specific component A to the decomposed matter A′ by way of the Nelson-Wagner method that is based on the primary decomposition reaction and obtaining the elution ratio.
FIG. 10 shows a measurement example of decomposed matter A′ by way of the Nelson-Wagner method. This method calculates the volume of change from the specific component A to the decomposed matter A′ from the reaction velocity and obtains an elution profile via simulation. Note that in this method the reaction of the specific component A changing into the decomposed matter A′ must be halted immediately after sampling, which makes the operation cumbersome.
In determination of a specific component in an elution test liquid by way of the absorbance measurement method, in case the preparation contains an impurity component having absorption in the ultraviolet or visible area other than the specific component, it is difficult to selectively determine the specific component alone. Further, in case the specific component easily changes in the test liquid, a precise elution volume is not determined. In the determination of the specific component in an elution test liquid by using the liquid chromatography, the reaction of the specific component must be halted through pH adjustment immediately after the sampling, which adds to cumbersome operation.